The present invention relates generally to the field of artificial organs, and more particularly to an artificial gut and method therefore.
In the medical environment, it is often desirable to have apparatus that mimic human organs. Such apparatus can be used, for example, to study the organ and its reaction to agents, to produce cells, tissues, or other materials, or to treat patients whose human organ is failing.
Artificial organs, such as, kidney, liver, lung, and pancreas, have been described in the art. Furthermore, a model of a digestive tract that simulates peristaltic movements that move the contents of the intestine onward has been described. There is not known, however, an artificial gut that adequately mimics the anatomy, morphology, and function of the mammalian small intestine, especially the absorption of nutrients from the contents of the intestine into the blood stream.
A need therefore exists for an artificial gut, and a method of manufacture and use therefore, that mimics the anatomy, morphology, and function of the mammalian small intestine.
The artificial gut, and method of manufacture and use therefore, described herein provides advantages over a mechanical gut in that it tends to mimic the anatomy, morphology, and function of the mammalian small intestine.
According to the present invention, the foregoing advantages are principally provided by an artificial gut that comprises a first hollow fiber having an inner surface that is lined with at least a portion of a layer of one or more of a plurality of biological components that typically line a mammalian gut. Further, a second hollow fiber is adjacent to the first hollow fiber.
In accordance with another aspect of the invention, the layer of one or more of the plurality of biological components consists essentially of enterocytes. The enterocyte-lined inner surface is perfused with a feeding solution containing nutrients, and the enterocytes absorb, process, and transport the nutrients across the wall of the first hollow fiber. The nutrients eventually diffuse into the second hollow fiber. A perfusate selected from the group consisting of culture medium, blood, and plasma, can perfuse an inner surface of the second hollow fiber, whereby the perfusate is nourished by the nutrients.
In another aspect of the invention, there can be a first system of a plurality of hollow fibers and a second system of a plurality of hollow fibers contained in a housing. The housing and outer surfaces of the first system of hollow fibers and the second system of hollow fibers define an extra-fiber space. The housing includes a first set of perfusion ports coupled with the first system of hollow fibers, and a second set of perfusion ports coupled with the second system of hollow fibers.
According to another aspect of the invention, the enterocytes lining the first system of hollow fibers absorb the nutrients and pass them into the extra-fiber space. The nutrients in the extra-fiber space then diffuse into the second system of hollow fibers.
In accordance with the method of manufacture of this invention, providing a first system of a plurality of hollow, porous fibers and a second system of a plurality of hollow, porous fibers, and lining the inner surface of each of the plurality of hollow, porous fibers of the first system with a layer of one or more of a plurality of biological components that line a mammalian gut.
In accordance with the method of using of this invention, providing an artificial gut including a first system of a plurality of hollow fibers and a second system of a plurality of hollow fibers, and lining the inner surface of each of the plurality of hollow fibers of the first system with a layer of one or more of the plurality of biological components. The lined inner surface of each of the plurality of hollow fibers of the first system is perfused with a first perfusate, and the inner surface of each of the plurality of hollow fibers of the second system is perfused with a second perfusate.
The method more particularly comprises the substeps of seeding the first system of a plurality of hollow fibers with the one or more of the plurality of biological components, and perfusing the outer surface of each of the plurality of hollow fibers of the first system with an oxygenated cell culture medium enriched with humoral components. The humoral components maintain viability and morphological integrity of the plurality of the biological components, and facilitate or enhance their function.
Additional advantages and novel features of the invention will be set forth in part in the description which follows, wherein only the preferred embodiments of the invention are shown and described, and in part become apparent to those skilled in the art upon examination of the following detailed description or may be learned by practice of the invention. The advantages of the invention may be realized and attained by means of the instrumentalities and combinations particularly pointed out in the appended claims.